Smooth solvation method for d-orbital semiempirical calculations of biological reactions. 2. Application to transphosphorylation thio effects in solution.
Smooth solvation method for d-orbital semiempirical calculations of biological reactions. 2. Application to transphosphorylation thio effects in solution.
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用于生物反应 d 轨道半经验计算的平滑溶剂化方法。
DOI：
10.1021/jp044061l
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
York,DarrinM
中科院分区：
文献类型：
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作者：
Gregersen,BrentA;Khandogin,Jana;Thiel,Walter;York,DarrinM
应用密度泛函和半经验量子方法以及连续介质和显式溶剂化模型研究了溶剂化对天然和硫代转磷酸化反应稳定性的作用。对不同方法获得的结果进行了广泛的比较。对于半经验方法，显式溶剂化处理使用混合量子力学/分子力学（QM/MM）的方法和隐式溶剂化处理使用最近开发的光滑溶剂化模型实施到d-轨道半经验框架（MNDO/d-SCOSMO）CHARMM内。将不同的量子和溶剂化方法应用于3 '-核糖，5'-甲基磷酸二酯的酯交换反应，该酯交换反应用作锤头状和发夹状核酶催化的自切割反应的非酶模型。硫代效应进行了研究的非桥磷酰氧位置的双硫取代。从MNDO/d-SCOSMO计算的本地和双硫取代反应的反应曲线是类似的QM/MM的结果，并与实验观察到的趋势一致。这些结果强调了需要磷和硫的d轨道半经验表示来研究酶促和非酶促磷酰基转移反应中实验观察到的硫代效应。本方法的主要优点之一是，它可以被应用到模型化学反应在显着较低的计算成本比密度泛函计算与隐式溶剂化或半经验QM/MM模拟与显式溶剂。
Density-functional and semiempirical quantum methods and continuum dielectric and explicit solvation models are applied to study the role of solvation on the stabilization of native and thio-substituted transphosphorylation reactions. Extensive comparison is made between results obtained from the different methods. For the semiempirical methods, explicit solvation was treated using a hybrid quantum mechanical/molecular mechanical (QM/MM) approach and the implicit solvation was treated using a recently developed smooth solvation model implemented into a d-orbital semiempirical framework (MNDO/d-SCOSMO) within CHARMM. The different quantum and solvation methods were applied to the transesterification of a 3‘-ribose,5‘-methyl phosphodiester that serves as a nonenzymatic model for the self-cleavage reaction catalyzed by the hammerhead and hairpin ribozymes. Thio effects were studied for a double sulfur substitution at the nonbridging phosphoryl oxygen positions. The reaction profiles of both the native and double sulfur-substituted reactions from the MNDO/d-SCOSMO calculations were similar to the QM/MM results and consistent with the experimentally observed trends. These results underscore the need for a d-orbital semiempirical representation for phosphorus and sulfur for the study of experimentally observed thio effects in enzymatic and nonenzymatic phosphoryl transfer reactions. One of the major advantages of the present approach is that it can be applied to model chemical reactions at a significantly lower computational cost than either the density-functional calculations with implicit solvation or the semiempirical QM/MM simulations with explicit solvent.